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Reduction of Rapid Proliferating Tumour Cell Lines by Inhibition of the Specific Glycine Transporter GLYT1

Lookup NU author(s): Dr Alison Howard, Emeritus Professor Barry Hirst

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This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


Abstract

Studies have highlighted the relevance of extracellular glycine and serine in supporting high growth rates of rapidly proliferating tumours. The present study analysed the role of the specific glycine transporter GLYT1 in supplying glycine to cancer cells and maintaining cell proliferation. GLYT1 knockdown in the rapidly proliferating tumour cell lines A549 and HT29 reduced the number of viable cells by approximately 30% and the replication rate presented a decrease of about 50% when compared to cells transfected with control siRNA. In contrast, when compared to control, GLYT1 siRNA had only a minimal effect on cell number of the slowly proliferating tumour cell line A498, reducing the number of viable cells by 7% and no significant difference was observed when analysing the replication rate between GLYT1 knockdown and control group. When utilising a specific GLYT1 inhibitor, ALX-5407, the doubling time of rapidly proliferating cells increased by about 8 h presenting a significant reduction in the number of viable cells after 96 h treatment when compared to untreated cells. Therefore, these results suggest that GLYT1 is required to maintain high proliferation rates in rapidly proliferating cancer cells and encourage further investigation of GLYT1 as a possible target in a novel therapeutic approach.


Publication metadata

Author(s): Bierhals CG, Howard A, Hirst BH

Publication type: Article

Publication status: Published

Journal: Biomedicines

Year: 2021

Volume: 9

Issue: 12

Online publication date: 25/11/2021

Acceptance date: 21/11/2021

Date deposited: 03/12/2021

ISSN (electronic): 2227-9059

Publisher: MDPI

URL: https://doi.org/10.3390/biomedicines9121770

DOI: 10.3390/biomedicines9121770


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Funding

Funder referenceFunder name
BEX 11910/13-5

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